In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection
New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishma...
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Elsevier
2019-01-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332218367878 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Débora V.C. Mendonça Grasiele S.V. Tavares Daniela P. Lage Tauane G. Soyer Lívia M. Carvalho Daniel S. Dias Patrícia A.F. Ribeiro Flaviano M. Ottoni Luciana M.R. Antinarelli Danniele L. Vale Fernanda Ludolf Mariana C. Duarte Elaine S. Coimbra Miguel A. Chávez-Fumagalli Bruno M. Roatt Daniel Menezes-Souza José Mário Barichello Ricardo J. Alves Eduardo A.F. Coelho |
spellingShingle |
Débora V.C. Mendonça Grasiele S.V. Tavares Daniela P. Lage Tauane G. Soyer Lívia M. Carvalho Daniel S. Dias Patrícia A.F. Ribeiro Flaviano M. Ottoni Luciana M.R. Antinarelli Danniele L. Vale Fernanda Ludolf Mariana C. Duarte Elaine S. Coimbra Miguel A. Chávez-Fumagalli Bruno M. Roatt Daniel Menezes-Souza José Mário Barichello Ricardo J. Alves Eduardo A.F. Coelho In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection Biomedicine & Pharmacotherapy Tegumentary leishmaniasis Chemotherapy Toxicity Amphotericin B Pluronic®F127 2-(2,3,4-Tri-O-acetyl-6-deoxy-β-l-galactopyranosyloxy)-1,4-naphthoquinone |
author_facet |
Débora V.C. Mendonça Grasiele S.V. Tavares Daniela P. Lage Tauane G. Soyer Lívia M. Carvalho Daniel S. Dias Patrícia A.F. Ribeiro Flaviano M. Ottoni Luciana M.R. Antinarelli Danniele L. Vale Fernanda Ludolf Mariana C. Duarte Elaine S. Coimbra Miguel A. Chávez-Fumagalli Bruno M. Roatt Daniel Menezes-Souza José Mário Barichello Ricardo J. Alves Eduardo A.F. Coelho |
author_sort |
Débora V.C. Mendonça |
title |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection |
title_short |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection |
title_full |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection |
title_fullStr |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection |
title_full_unstemmed |
In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection |
title_sort |
in vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a pluronic® f127-based polymeric micelle system against leishmania amazonensis infection |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-01-01 |
description |
New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome®, Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL-10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis. |
topic |
Tegumentary leishmaniasis Chemotherapy Toxicity Amphotericin B Pluronic®F127 2-(2,3,4-Tri-O-acetyl-6-deoxy-β-l-galactopyranosyloxy)-1,4-naphthoquinone |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218367878 |
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doaj-e7491b6934e34937acd1c17a6771ef902021-05-21T04:16:52ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-01-01109779787In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infectionDébora V.C. Mendonça0Grasiele S.V. Tavares1Daniela P. Lage2Tauane G. Soyer3Lívia M. Carvalho4Daniel S. Dias5Patrícia A.F. Ribeiro6Flaviano M. Ottoni7Luciana M.R. Antinarelli8Danniele L. Vale9Fernanda Ludolf10Mariana C. Duarte11Elaine S. Coimbra12Miguel A. Chávez-Fumagalli13Bruno M. Roatt14Daniel Menezes-Souza15José Mário Barichello16Ricardo J. Alves17Eduardo A.F. Coelho18Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilLaboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, 35400-000, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, BrazilDepartamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, 36036-900, Juiz de Fora, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, BrazilLaboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, 35400-000, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, BrazilLaboratório de Tecnologia Farmacêutica, Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Universidade Federal de Pelotas. 96900-010, Pelotas, Rio Grande do Sul, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, BrazilPrograma de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, Brazil; Corresponding author at: Laboratório de Pesquisa do Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, sala 143, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Prof. Alfredo Balena, 190, 30.130-100, Belo Horizonte, Minas Gerais, Brazil.New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome®, Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL-10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis.http://www.sciencedirect.com/science/article/pii/S0753332218367878Tegumentary leishmaniasisChemotherapyToxicityAmphotericin BPluronic®F1272-(2,3,4-Tri-O-acetyl-6-deoxy-β-l-galactopyranosyloxy)-1,4-naphthoquinone |